Differential Interaction of the Two Related Fungal SpeciesCandida albicansandCandida dubliniensiswith Human Neutrophils

Abstract

Candida albicans, the most common facultative human pathogenic fungus is of major medical importance, whereas the closely related species Candida dubliniensis is less virulent and rarely causes life-threatening, systemic infections. Little is known, however, about the reasons for this difference in pathogenicity, and especially on the interactions of C. dubliniensis with the human immune system. Because innate immunity and, in particular, neutrophil granulocytes play a major role in host antifungal defense, we studied the responses of human neutrophils to clinical isolates of both C. albicans and C. dubliniensis. C. dubliniensis was found to support neutrophil migration and fungal cell uptake to a greater extent in comparison with C. albicans, whereas inducing less neutrophil damage and extracellular trap formation. The production of antimicrobial reactive oxygen species, myeloperoxidase, and lactoferrin, as well as the inflammatory chemokine IL-8 by neutrophils was increased when stimulated with C. dubliniensis as compared with C. albicans. However, most of the analyzed macrophage-derived inflammatory and regulatory cytokines and chemokines, such as IL-1α, IL-1β, IL-1ra, TNF-α, IL-10, G-CSF, and GM-CSF, were less induced by C. dubliniensis. Similarly, the amounts of the antifungal immunity-related IL-17A produced by PBMCs was significantly lower when challenged with C. dubliniensis than with C. albicans. These data indicate that C. dubliniensis triggers stronger early neutrophil responses than C. albicans, thus providing insight into the differential virulence of these two closely related fungal species, and suggest that this is, in part, due to their differential capacity to form hyphae.

Complement factor H modulates the activation of human neutrophil granulocytes and the generation of neutrophil extracellular traps

“…Neutrophils are not simply effective and fast killer/effector cells, but depending on the size and nature of the pathogen they deploy different antimicrobial responses. They can selectively release NETs in response to fungal hyphae and pathogens, which are too large to be phagocytosed (Branzk et al, 2014;Byrd et al, 2013;Svobodova et al, 2012). These DNA-based, web-like structures have effective trapping function and are able to prevent pathogen expansion and dissemination.…”

Impaired PRR expression modulates inflammation-triggered oxidative stress and pathogenesis of recurrent vulvovaginal infections

“…Reactive oxidants have been suggested to be involved in various defense mechanisms against pathogens, leading to the state of oxidative stress, with significant biological consequences (Lugrin et al, 2014). Different studies have documented high ROS production by neutrophils in response to BV-associated bacteria, C. albicans, and T. vaginalis infection and suggested to play an important role in maintaining low burden of infection (Li et al, 2012b; de Souza Bonfim-Mendonça P, Ratti BA, Godoy JD, 2014; Frasson et al, 2012;Svobodová et al, 2012;Johnson et al, 2017). To assess the status of oxidative stress by studying all oxidants/anti-oxidants parameters is tedious, time-consuming, and uneconomical.…”

Hematogenous dissemination of Candida dubliniensis causing spondylodiscitis and spinal abscess in a HIV-1 and HCV-coinfected patient

“…The innate immunity represented by neutrophils and macrophages is believed to serve as the first line of defense by phagocytosis and direct killing of Candida . Furthermore, the antifungal immunity-related IL-17A, which is considered an important component in host defense against Candida infections, produced by peripheral blood mononuclear cells is significantly lower when challenged with C. dubliniensis in vitro [18]. Recently, Krause and colleagues even showed that candidemic patients had significantly higher IL-17A levels compared to non-candidemic patients [19].…”